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Yin, H. ; Karayel, O.* ; Chao, Y.Y.* ; Seeholzer, T. ; Hamp, I. ; Plettenburg, O. ; Gehring, T. ; Zielinski, C.* ; Mann, M.* ; Krappmann, D.

A20 and ABIN-1 cooperate in balancing CBM complex-triggered NF-κB signaling in activated T cells.

Cell. Mol. Life Sci. 79:112 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
T cell activation initiates protective adaptive immunity, but counterbalancing mechanisms are critical to prevent overshooting responses and to maintain immune homeostasis. The CARD11-BCL10-MALT1 (CBM) complex bridges T cell receptor engagement to NF-κB signaling and MALT1 protease activation. Here, we show that ABIN-1 is modulating the suppressive function of A20 in T cells. Using quantitative mass spectrometry, we identified ABIN-1 as an interactor of the CBM signalosome in activated T cells. A20 and ABIN-1 counteract inducible activation of human primary CD4 and Jurkat T cells. While A20 overexpression is able to silence CBM complex-triggered NF-κB and MALT1 protease activation independent of ABIN-1, the negative regulatory function of ABIN-1 depends on A20. The suppressive function of A20 in T cells relies on ubiquitin binding through the C-terminal zinc finger (ZnF)4/7 motifs, but does not involve the deubiquitinating activity of the OTU domain. Our mechanistic studies reveal that the A20/ABIN-1 module is recruited to the CBM complex via A20 ZnF4/7 and that proteasomal degradation of A20 and ABIN-1 releases the CBM complex from the negative impact of both regulators. Ubiquitin binding to A20 ZnF4/7 promotes destructive K48-polyubiquitination to itself and to ABIN-1. Further, after prolonged T cell stimulation, ABIN-1 antagonizes MALT1-catalyzed cleavage of re-synthesized A20 and thereby diminishes sustained CBM complex signaling. Taken together, interdependent post-translational mechanisms are tightly controlling expression and activity of the A20/ABIN-1 silencing module and the cooperative action of both negative regulators is critical to balance CBM complex signaling and T cell activation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Carma1 ; Immune Activation ; Immune Suppression ; T Cell Signaling ; Tnfaip3 ; Tnip1; Modifying Enzyme A20; Ubiquitin-binding; A20-binding Inhibitor; Linear Polyubiquitin; Malt1 Paracaspase; Receptor; Inflammation; Lymphocytes; Recruitment; Expression
ISSN (print) / ISBN 1420-682X
e-ISSN 1420-9071
Zeitschrift Cellular and Molecular Life Sciences - CMLS
Quellenangaben Band: 79, Heft: 2, Seiten: , Artikelnummer: 112 Supplement: ,
Verlag Birkhäuser
Verlagsort Picassoplatz 4, Basel, 4052, Switzerland
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Signaling and Translation (SAT)
Institute of Molecular Toxicology and Pharmacology (TOXI)
Institute of Medicinal Chemistry (IMC)
Förderungen Deutsche Forschungsgemeinschaft